A Pilot Trial Comparing Full Dose Rivaroxaban to Prophylactic Dose Rivaroxaban in Patients With Superficial Vein Thrombosis in the Leg

Official title

A Pilot Randomized Double-Blinded Comparison of Full Treatment Dose Rivaroxaban for 90 Days to Prophylactic Dose Rivaroxaban for 45 Days in Patients With Lower Extremity Superficial Vein Thrombosis

Overview

The goal of this clinical trial, called a pilot study or a feasibility study, is to test the study plan and to find out whether enough participants will join a larger study and accept the study procedures. This type of study includes a small number of participants so it is not expected to prove how safe the treatment is or how well the treatment works. The main question it hopes to answer is: 1.What is the average number of patients that are recruited per month during the 12 month study period? To test the study plan, adults being treated for a superficial vein thrombosis (SVT), which is a blood clot in the superficial veins of the leg, will be given a type of blood thinner called rivaroxaban. Half of the participants in this study will be given the standard (low-dose) rivaroxaban for 45 days, then 45 days of placebo (a substance that looks like the study medication but does not have any active or medicinal ingredients). The other half of participants will be given full-dose rivaroxaban for a total of 90 days. The placebo in this study is not intended to have any effect on the participants blood clot. A placebo is used to make the results of the study more reliable.

Detailed description

The standard or usual treatment for a superficial vein thrombosis (SVT) is to treat with a low-dose (often called a prophylactic dose) of blood thinner for 45 days. Rivaroxaban is a type of oral blood thinner that is used in the treatment and prevention of blood clots. Currently, rivaroxaban 10mg daily for 45 days is the most commonly used treatment in patients with lower extremity SVT.

Recent studies of participants with SVT suggest that treatment with full-dose (sometimes called therapeutic dose) blood thinners could be promising in preventing additional complications from SVT such as:

* A new blood clot in the deep veins of the legs or arms * A new pulmonary embolism (a blood clot in the lungs) * A recurrence or extension of the existing SVT (the existing clot comes back after treatment is stopped or gets bigger)

The Investigators are studying whether a full-dose of rivaroxaban for 90 days could prevent or improve additional complications from SVT.

Interventions

• Drug Full dose rivaroxaban
  The intervention group will receive full dose rivaroxaban for 90 days.
• Drug Low dose rivaroxaban
  The comparator group will receive the standard treatment of low dose rivaroxaban.
• Drug Placebo
  Since the treatment arm has an AM and PM dose of study drug from Day 1-21, the comparator group will take 1 placebo pill in the PM to keep the two arms blinded.

Primary outcome measures

• Primary Feasibility Outcome [Time frame: 12 months from when recruitment opens.]

Secondary outcome measures (4)

• Secondary Feasibility Outcomes [Time frame: From the start of study recruitment to the last follow-up of the last participant enrolled.]
• Secondary Feasibility Outcomes [Time frame: From the start of study recruitment to the last follow-up of the last participant enrolled.]
• Secondary Feasibility Outcomes [Time frame: From the start of study recruitment to the last follow-up of the last participant enrolled.]
• Secondary Feasibility Outcomes [Time frame: From the start of study recruitment to the last follow-up of the last participant enrolled.]

Eligibility criteria

Inclusion criteria

• Adult patients age ≥ 18 years old.
• Objectively confirmed diagnosis within 14 days of an acute symptomatic SVT of the lower extremities by standardized CUS, where SVT is defined as incompressibility of a venous segment located along the course of a known superficial vein.
• Anticoagulation for SVT is warranted per clinicians.
• Able and willing to provide written informed consent.

Exclusion criteria

• Other indication(s) for therapeutic or prophylactic dose anticoagulation (e.g. atrial fibrillation, mechanical valve, etc.).
• History of PE or DVT within 6 months (180 days) of screening.
• >5 days of any anticoagulants for the index SVT.
• Requires use of aspirin >100mg daily or other antiplatelet agents.
• Patients receiving concomitant systemic treatment with strong inhibitors of both CYP 3A4 and P-gp (e.g. cobicistat, ketoconazole, itraconazole, posaconazole, ritanovir, etc.).
• Active bleeding or history of CRNMB or major bleeding (as defined by the ISTH) within 30 days of screening.
• History of severe head trauma or ophthalmic, spinal, cerebral surgery within 90 days of screening.
• Have acute endocarditis.
• Thrombocytopenia (platelet count <50,000/uL), acute hepatitis, chronic active hepatitis, cirrhosis with severe hepatic impairment defined by a Childs-Pugh class B or C.
• Creatinine clearance <30 ml/min.
• Known contraindication to treatment with rivaroxaban.
• Are participating in another interventional trial that would compromise the results or integrity of this trial as determined by the investigator.
• Pregnant or breast feeding.
• Known hereditary or acquired severe hemorrhagic disease.
• Life expectancy <3 months.
• Unstable medical or psychological condition that would interfere with trial participation at the discretion of the site investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Canada · 2 centers

• The Ottawa Hospital — Ottawa
• Hopital Montfort — Ottawa

Publications

• Beyer-Westendorf J, Schellong SM, Gerlach H, Rabe E, Weitz JI, Jersemann K, Sahin K, Bauersachs R; SURPRISE investigators. Prevention of thromboembolic complications in patients with superficial-vein thrombosis given rivaroxaban or fondaparinux: the open-label, randomised, non-inferiority SURPRISE phase 3b trial. Lancet Haematol. 2017 Mar;4(3):e105-e113. doi: 10.1016/S2352-3026(17)30014-5. Epub 20 PMID 28219692
• Samama MM. The mechanism of action of rivaroxaban--an oral, direct Factor Xa inhibitor--compared with other anticoagulants. Thromb Res. 2011 Jun;127(6):497-504. doi: 10.1016/j.thromres.2010.09.008. Epub 2010 Oct 2. PMID 20888031
• Blondon M, Righini M, Bounameaux H, Veenstra DL. Fondaparinux for isolated superficial vein thrombosis of the legs: a cost-effectiveness analysis. Chest. 2012 Feb;141(2):321-329. doi: 10.1378/chest.11-0625. Epub 2011 Jul 14. PMID 21757569
• Wichers IM, Di Nisio M, Buller HR, Middeldorp S. Treatment of superficial vein thrombosis to prevent deep vein thrombosis and pulmonary embolism: a systematic review. Haematologica. 2005 May;90(5):672-7. PMID 15921382
• Duffett L. Management of Superficial Venous Thrombosis: A Systematic Review of Literature and Survey of Canadian Physicians. Thesis. Université d'Ottawa / University of Ottawa; 2018. doi:10.20381/ruor-21377
• Duffett L, Kearon C, Rodger M, Carrier M. Treatment of Superficial Vein Thrombosis: A Systematic Review and Meta-Analysis. Thromb Haemost. 2019 Mar;119(3):479-489. doi: 10.1055/s-0039-1677793. Epub 2019 Feb 4. PMID 30716777
• Frappe P, Buchmuller-Cordier A, Bertoletti L, Bonithon-Kopp C, Couzan S, Lafond P, Leizorovicz A, Merah A, Presles E, Preynat P, Tardy B, Decousus H; STEPH Study Group. Annual diagnosis rate of superficial vein thrombosis of the lower limbs: the STEPH community-based study. J Thromb Haemost. 2014 Jun;12(6):831-8. doi: 10.1111/jth.12575. PMID 24679145
• Leon L, Giannoukas AD, Dodd D, Chan P, Labropoulos N. Clinical significance of superficial vein thrombosis. Eur J Vasc Endovasc Surg. 2005 Jan;29(1):10-7. doi: 10.1016/j.ejvs.2004.09.021. PMID 15570265

Identifiers

NCT: NCT06965998 · RIVA-SVT Pilot

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗